Project acronym 100 Archaic Genomes
Project Genome sequences from extinct hominins
Researcher (PI) Svante PÄÄBO
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Call Details Advanced Grant (AdG), LS2, ERC-2015-AdG
Summary Neandertals and Denisovans, an Asian group distantly related to Neandertals, are the closest evolutionary relatives of present-day humans. They are thus of direct relevance for understanding the origin of modern humans and how modern humans differ from their closest relatives. We will generate genome-wide data from a large number of Neandertal and Denisovan individuals from across their geographical and temporal range as well as from other extinct hominin groups which we may discover. This will be possible by automating highly sensitive approaches to ancient DNA extraction and DNA libraries construction that we have developed so that they can be applied to many specimens from many sites in order to identify those that contain retrievable DNA. Whenever possible we will sequence whole genomes and in other cases use DNA capture methods to generate high-quality data from representative parts of the genome. This will allow us to study the population history of Neandertals and Denisovans, elucidate how many times and where these extinct hominins contributed genes to present-day people, and the extent to which modern humans and archaic groups contributed genetically to Neandertals and Denisovans. By retrieving DNA from specimens that go back to the Middle Pleistocene we will furthermore shed light on the early history and origins of Neandertals and Denisovans.
Summary
Neandertals and Denisovans, an Asian group distantly related to Neandertals, are the closest evolutionary relatives of present-day humans. They are thus of direct relevance for understanding the origin of modern humans and how modern humans differ from their closest relatives. We will generate genome-wide data from a large number of Neandertal and Denisovan individuals from across their geographical and temporal range as well as from other extinct hominin groups which we may discover. This will be possible by automating highly sensitive approaches to ancient DNA extraction and DNA libraries construction that we have developed so that they can be applied to many specimens from many sites in order to identify those that contain retrievable DNA. Whenever possible we will sequence whole genomes and in other cases use DNA capture methods to generate high-quality data from representative parts of the genome. This will allow us to study the population history of Neandertals and Denisovans, elucidate how many times and where these extinct hominins contributed genes to present-day people, and the extent to which modern humans and archaic groups contributed genetically to Neandertals and Denisovans. By retrieving DNA from specimens that go back to the Middle Pleistocene we will furthermore shed light on the early history and origins of Neandertals and Denisovans.
Max ERC Funding
2 350 000 €
Duration
Start date: 2016-11-01, End date: 2021-10-31
Project acronym 2-HIT
Project Genetic interaction networks: From C. elegans to human disease
Researcher (PI) Ben Lehner
Host Institution (HI) FUNDACIO CENTRE DE REGULACIO GENOMICA
Call Details Starting Grant (StG), LS2, ERC-2007-StG
Summary Most hereditary diseases in humans are genetically complex, resulting from combinations of mutations in multiple genes. However synthetic interactions between genes are very difficult to identify in population studies because of a lack of statistical power and we fundamentally do not understand how mutations interact to produce phenotypes. C. elegans is a unique animal in which genetic interactions can be rapidly identified in vivo using RNA interference, and we recently used this system to construct the first genetic interaction network for any animal, focused on signal transduction genes. The first objective of this proposal is to extend this work and map a comprehensive genetic interaction network for this model metazoan. This project will provide the first insights into the global properties of animal genetic interaction networks, and a comprehensive view of the functional relationships between genes in an animal. The second objective of the proposal is to use C. elegans to develop and validate experimentally integrated gene networks that connect genes to phenotypes and predict genetic interactions on a genome-wide scale. The methods that we develop and validate in C. elegans will then be applied to predict phenotypes and interactions for human genes. The final objective is to dissect the molecular mechanisms underlying genetic interactions, and to understand how these interactions evolve. The combined aim of these three objectives is to generate a framework for understanding and predicting how mutations interact to produce phenotypes, including in human disease.
Summary
Most hereditary diseases in humans are genetically complex, resulting from combinations of mutations in multiple genes. However synthetic interactions between genes are very difficult to identify in population studies because of a lack of statistical power and we fundamentally do not understand how mutations interact to produce phenotypes. C. elegans is a unique animal in which genetic interactions can be rapidly identified in vivo using RNA interference, and we recently used this system to construct the first genetic interaction network for any animal, focused on signal transduction genes. The first objective of this proposal is to extend this work and map a comprehensive genetic interaction network for this model metazoan. This project will provide the first insights into the global properties of animal genetic interaction networks, and a comprehensive view of the functional relationships between genes in an animal. The second objective of the proposal is to use C. elegans to develop and validate experimentally integrated gene networks that connect genes to phenotypes and predict genetic interactions on a genome-wide scale. The methods that we develop and validate in C. elegans will then be applied to predict phenotypes and interactions for human genes. The final objective is to dissect the molecular mechanisms underlying genetic interactions, and to understand how these interactions evolve. The combined aim of these three objectives is to generate a framework for understanding and predicting how mutations interact to produce phenotypes, including in human disease.
Max ERC Funding
1 100 000 €
Duration
Start date: 2008-09-01, End date: 2014-04-30
Project acronym 2D-4-CO2
Project DESIGNING 2D NANOSHEETS FOR CO2 REDUCTION AND INTEGRATION INTO vdW HETEROSTRUCTURES FOR ARTIFICIAL PHOTOSYNTHESIS
Researcher (PI) Damien VOIRY
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), PE8, ERC-2018-STG
Summary CO2 reduction reaction (CO2RR) holds great promise for conversion of the green-house gas carbon dioxide into chemical fuels. The absence of catalytic materials demonstrating high performance and high selectivity currently hampers practical demonstration. CO2RR is also limited by the low solubility of CO2 in the electrolyte solution and therefore electrocatalytic reactions in gas phase using gas diffusion electrodes would be preferred. 2D materials have recently emerged as a novel class of electrocatalytic materials thanks to their rich structures and electronic properties. The synthesis of novel 2D catalysts and their implementation into photocatalytic systems would be a major step towards the development of devices for storing solar energy in the form of chemical fuels. With 2D-4-CO2, I propose to: 1) develop novel class of CO2RR catalysts based on conducting 2D nanosheets and 2) demonstrate photocatalytic conversion of CO2 into chemical fuels using structure engineered gas diffusion electrodes made of 2D conducting catalysts. To reach this goal, the first objective of 2D-4-CO2 is to provide guidelines for the development of novel cutting-edge 2D catalysts towards CO2 conversion into chemical fuel. This will be possible by using a multidisciplinary approach based on 2D materials engineering, advanced methods of characterization and novel designs of gas diffusion electrodes for the reduction of CO2 in gas phase. The second objective is to develop practical photocatalytic systems using van der Waals (vdW) heterostructures for the efficient conversion of CO2 into chemical fuels. vdW heterostructures will consist in rational designs of 2D materials and 2D-like materials deposited by atomic layer deposition in order to achieve highly efficient light conversion and prolonged stability. This project will not only enable a deeper understanding of the CO2RR but it will also provide practical strategies for large-scale application of CO2RR for solar fuel production.
Summary
CO2 reduction reaction (CO2RR) holds great promise for conversion of the green-house gas carbon dioxide into chemical fuels. The absence of catalytic materials demonstrating high performance and high selectivity currently hampers practical demonstration. CO2RR is also limited by the low solubility of CO2 in the electrolyte solution and therefore electrocatalytic reactions in gas phase using gas diffusion electrodes would be preferred. 2D materials have recently emerged as a novel class of electrocatalytic materials thanks to their rich structures and electronic properties. The synthesis of novel 2D catalysts and their implementation into photocatalytic systems would be a major step towards the development of devices for storing solar energy in the form of chemical fuels. With 2D-4-CO2, I propose to: 1) develop novel class of CO2RR catalysts based on conducting 2D nanosheets and 2) demonstrate photocatalytic conversion of CO2 into chemical fuels using structure engineered gas diffusion electrodes made of 2D conducting catalysts. To reach this goal, the first objective of 2D-4-CO2 is to provide guidelines for the development of novel cutting-edge 2D catalysts towards CO2 conversion into chemical fuel. This will be possible by using a multidisciplinary approach based on 2D materials engineering, advanced methods of characterization and novel designs of gas diffusion electrodes for the reduction of CO2 in gas phase. The second objective is to develop practical photocatalytic systems using van der Waals (vdW) heterostructures for the efficient conversion of CO2 into chemical fuels. vdW heterostructures will consist in rational designs of 2D materials and 2D-like materials deposited by atomic layer deposition in order to achieve highly efficient light conversion and prolonged stability. This project will not only enable a deeper understanding of the CO2RR but it will also provide practical strategies for large-scale application of CO2RR for solar fuel production.
Max ERC Funding
1 499 931 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym 2DNANOCAPS
Project Next Generation of 2D-Nanomaterials: Enabling Supercapacitor Development
Researcher (PI) Valeria Nicolosi
Host Institution (HI) THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN
Call Details Starting Grant (StG), PE8, ERC-2011-StG_20101014
Summary Climate change and the decreasing availability of fossil fuels require society to move towards sustainable and renewable resources. 2DNanoCaps will focus on electrochemical energy storage, specifically supercapacitors. In terms of performance supercapacitors fill up the gap between batteries and the classical capacitors. Whereas batteries possess a high energy density but low power density, supercapacitors possess high power density but low energy density. Efforts are currently dedicated to move supercapacitors towards high energy density and high power density performance. Improvements have been achieved in the last few years due to the use of new electrode nanomaterials and the design of new hybrid faradic/capacitive systems. We recognize, however, that we are reaching a newer limit beyond which we will only see small incremental improvements. The main reason for this being the intrinsic difficulty in handling and processing materials at the nano-scale and the lack of communication across different scientific disciplines. I plan to use a multidisciplinary approach, where novel nanomaterials, existing knowledge on nano-scale processing and established expertise in device fabrication and testing will be brought together to focus on creating more efficient supercapacitor technologies. 2DNanoCaps will exploit liquid phase exfoliated two-dimensional nanomaterials such as transition metal oxides, layered metal chalcogenides and graphene as electrode materials. Electrodes will be ultra-thin (capacitance and thickness of the electrodes are inversely proportional), conductive, with high dielectric constants. Intercalation of ions between the assembled 2D flakes will be also achievable, providing pseudo-capacitance. The research here proposed will be initially based on fundamental laboratory studies, recognising that this holds the key to achieving step-change in supercapacitors, but also includes scaling-up and hybridisation as final objectives.
Summary
Climate change and the decreasing availability of fossil fuels require society to move towards sustainable and renewable resources. 2DNanoCaps will focus on electrochemical energy storage, specifically supercapacitors. In terms of performance supercapacitors fill up the gap between batteries and the classical capacitors. Whereas batteries possess a high energy density but low power density, supercapacitors possess high power density but low energy density. Efforts are currently dedicated to move supercapacitors towards high energy density and high power density performance. Improvements have been achieved in the last few years due to the use of new electrode nanomaterials and the design of new hybrid faradic/capacitive systems. We recognize, however, that we are reaching a newer limit beyond which we will only see small incremental improvements. The main reason for this being the intrinsic difficulty in handling and processing materials at the nano-scale and the lack of communication across different scientific disciplines. I plan to use a multidisciplinary approach, where novel nanomaterials, existing knowledge on nano-scale processing and established expertise in device fabrication and testing will be brought together to focus on creating more efficient supercapacitor technologies. 2DNanoCaps will exploit liquid phase exfoliated two-dimensional nanomaterials such as transition metal oxides, layered metal chalcogenides and graphene as electrode materials. Electrodes will be ultra-thin (capacitance and thickness of the electrodes are inversely proportional), conductive, with high dielectric constants. Intercalation of ions between the assembled 2D flakes will be also achievable, providing pseudo-capacitance. The research here proposed will be initially based on fundamental laboratory studies, recognising that this holds the key to achieving step-change in supercapacitors, but also includes scaling-up and hybridisation as final objectives.
Max ERC Funding
1 501 296 €
Duration
Start date: 2011-10-01, End date: 2016-09-30
Project acronym 2G-CSAFE
Project Combustion of Sustainable Alternative Fuels for Engines used in aeronautics and automotives
Researcher (PI) Philippe Dagaut
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Advanced Grant (AdG), PE8, ERC-2011-ADG_20110209
Summary This project aims at promoting sustainable combustion technologies for transport via validation of advanced combustion kinetic models obtained using sophisticated new laboratory experiments, engines, and theoretical computations, breaking through the current frontier of knowledge. It will focus on the unexplored kinetics of ignition and combustion of 2nd generation (2G) biofuels and blends with conventional fuels, which should provide energy safety and sustainability to Europe. The motivation is that no accurate kinetic models are available for the ignition, oxidation and combustion of 2G-biofuels, and improved ignition control is needed for new compression ignition engines. Crucial information is missing: data from well characterised experiments on combustion-generated pollutants and data on key-intermediates for fuels ignition in new engines.
To provide that knowledge new well-instrumented complementary experiments and kinetic modelling will be used. Measurements of key-intermediates, stables species, and pollutants will be performed. New ignition control strategies will be designed, opening new technological horizons. Kinetic modelling will be used for rationalising the results. Due to the complexity of 2G-biofuels and their unusual composition, innovative surrogates will be designed. Kinetic models for surrogate fuels will be generalised for extension to other compounds. The experimental results, together with ab-initio and detailed modelling, will serve to characterise the kinetics of ignition, combustion, and pollutants formation of fuels including 2G biofuels, and provide relevant data and models.
This research is risky because this is (i) the 1st effort to measure radicals by reactor/CRDS coupling, (ii) the 1st effort to use a μ-channel reactor to build ignition databases for conventional and bio-fuels, (iii) the 1st effort to design and use controlled generation and injection of reactive species to control ignition/combustion in compression ignition engines
Summary
This project aims at promoting sustainable combustion technologies for transport via validation of advanced combustion kinetic models obtained using sophisticated new laboratory experiments, engines, and theoretical computations, breaking through the current frontier of knowledge. It will focus on the unexplored kinetics of ignition and combustion of 2nd generation (2G) biofuels and blends with conventional fuels, which should provide energy safety and sustainability to Europe. The motivation is that no accurate kinetic models are available for the ignition, oxidation and combustion of 2G-biofuels, and improved ignition control is needed for new compression ignition engines. Crucial information is missing: data from well characterised experiments on combustion-generated pollutants and data on key-intermediates for fuels ignition in new engines.
To provide that knowledge new well-instrumented complementary experiments and kinetic modelling will be used. Measurements of key-intermediates, stables species, and pollutants will be performed. New ignition control strategies will be designed, opening new technological horizons. Kinetic modelling will be used for rationalising the results. Due to the complexity of 2G-biofuels and their unusual composition, innovative surrogates will be designed. Kinetic models for surrogate fuels will be generalised for extension to other compounds. The experimental results, together with ab-initio and detailed modelling, will serve to characterise the kinetics of ignition, combustion, and pollutants formation of fuels including 2G biofuels, and provide relevant data and models.
This research is risky because this is (i) the 1st effort to measure radicals by reactor/CRDS coupling, (ii) the 1st effort to use a μ-channel reactor to build ignition databases for conventional and bio-fuels, (iii) the 1st effort to design and use controlled generation and injection of reactive species to control ignition/combustion in compression ignition engines
Max ERC Funding
2 498 450 €
Duration
Start date: 2011-12-01, End date: 2016-11-30
Project acronym 3D-E
Project 3D Engineered Environments for Regenerative Medicine
Researcher (PI) Ruth Elizabeth Cameron
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Advanced Grant (AdG), PE8, ERC-2012-ADG_20120216
Summary "This proposal develops a unified, underpinning technology to create novel, complex and biomimetic 3D environments for the control of tissue growth. As director of Cambridge Centre for Medical Materials, I have recently been approached by medical colleagues to help to solve important problems in the separate therapeutic areas of breast cancer, cardiac disease and blood disorders. In each case, the solution lies in complex 3D engineered environments for cell culture. These colleagues make it clear that existing 3D scaffolds fail to provide the required complex orientational and spatial anisotropy, and are limited in their ability to impart appropriate biochemical and mechanical cues.
I have a strong track record in this area. A particular success has been the use of a freeze drying technology to make collagen based porous implants for the cartilage-bone interface in the knee, which has now been commercialised. The novelty of this proposal lies in the broadening of the established scientific base of this technology to enable biomacromolecular structures with:
(A) controlled and complex pore orientation to mimic many normal multi-oriented tissue structures
(B) compositional and positional control to match varying local biochemical environments,
(C) the attachment of novel peptides designed to control cell behaviour, and
(D) mechanical control at both a local and macroscopic level to provide mechanical cues for cells.
These will be complemented by the development of
(E) robust characterisation methodologies for the structures created.
These advances will then be employed in each of the medical areas above.
This approach is highly interdisciplinary. Existing working relationships with experts in each medical field will guarantee expertise and licensed facilities in the required biological disciplines. Funds for this proposal would therefore establish a rich hub of mutually beneficial research and opportunities for cross-disciplinary sharing of expertise."
Summary
"This proposal develops a unified, underpinning technology to create novel, complex and biomimetic 3D environments for the control of tissue growth. As director of Cambridge Centre for Medical Materials, I have recently been approached by medical colleagues to help to solve important problems in the separate therapeutic areas of breast cancer, cardiac disease and blood disorders. In each case, the solution lies in complex 3D engineered environments for cell culture. These colleagues make it clear that existing 3D scaffolds fail to provide the required complex orientational and spatial anisotropy, and are limited in their ability to impart appropriate biochemical and mechanical cues.
I have a strong track record in this area. A particular success has been the use of a freeze drying technology to make collagen based porous implants for the cartilage-bone interface in the knee, which has now been commercialised. The novelty of this proposal lies in the broadening of the established scientific base of this technology to enable biomacromolecular structures with:
(A) controlled and complex pore orientation to mimic many normal multi-oriented tissue structures
(B) compositional and positional control to match varying local biochemical environments,
(C) the attachment of novel peptides designed to control cell behaviour, and
(D) mechanical control at both a local and macroscopic level to provide mechanical cues for cells.
These will be complemented by the development of
(E) robust characterisation methodologies for the structures created.
These advances will then be employed in each of the medical areas above.
This approach is highly interdisciplinary. Existing working relationships with experts in each medical field will guarantee expertise and licensed facilities in the required biological disciplines. Funds for this proposal would therefore establish a rich hub of mutually beneficial research and opportunities for cross-disciplinary sharing of expertise."
Max ERC Funding
2 486 267 €
Duration
Start date: 2013-04-01, End date: 2018-03-31
Project acronym 3D-FABRIC
Project 3D Flow Analysis in Bijels Reconfigured for Interfacial Catalysis
Researcher (PI) Martin F. HAASE
Host Institution (HI) UNIVERSITEIT UTRECHT
Call Details Starting Grant (StG), PE8, ERC-2018-STG
Summary The objective of this proposal is to determine the unknown criteria for convective cross-flow in bicontinuous interfacially jammed emulsion gels (bijels). Based on this, we will answer the question: Can continuously operated interfacial catalysis be realized in bijel cross-flow reactors? Demonstrating this potential will introduce a broadly applicable chemical technology, replacing wasteful chemical processes that require organic solvents. We will achieve our objective in three steps:
(a) Control over bijel structure and properties. Bijels will be formed with a selection of functional inorganic colloidal particles. Nanoparticle surface modifications will be developed and extensively characterized. General principles for the parameters determining bijel structures and properties will be established based on confocal and electron microscopy characterization. These principles will enable unprecedented control over bijel formation and will allow for designing desired properties.
(b) Convective flow in bijels. The mechanical strength of bijels will be tailored and measured. With mechanically robust bijels, the influence of size and organization of oil/water channels on convective mass transfer in bijels will be investigated. To this end, a bijel mass transfer apparatus fabricated by 3d-printing of bijel fibers and soft photolithography will be introduced. In conjunction with the following objective, the analysis of convective flows in bijels will facilitate a thorough description of their structure/function relationships.
(c) Biphasic chemical reactions in STrIPS bijel cross-flow reactors. First, continuous extraction in bijels will be realized. Next, conditions to carry out continuously-operated, phase transfer catalysis of well-known model reactions in bijels will be determined. Both processes will be characterized in-situ and in 3-dimensions by confocal microscopy of fluorescent phase transfer reactions in transparent bijels.
Summary
The objective of this proposal is to determine the unknown criteria for convective cross-flow in bicontinuous interfacially jammed emulsion gels (bijels). Based on this, we will answer the question: Can continuously operated interfacial catalysis be realized in bijel cross-flow reactors? Demonstrating this potential will introduce a broadly applicable chemical technology, replacing wasteful chemical processes that require organic solvents. We will achieve our objective in three steps:
(a) Control over bijel structure and properties. Bijels will be formed with a selection of functional inorganic colloidal particles. Nanoparticle surface modifications will be developed and extensively characterized. General principles for the parameters determining bijel structures and properties will be established based on confocal and electron microscopy characterization. These principles will enable unprecedented control over bijel formation and will allow for designing desired properties.
(b) Convective flow in bijels. The mechanical strength of bijels will be tailored and measured. With mechanically robust bijels, the influence of size and organization of oil/water channels on convective mass transfer in bijels will be investigated. To this end, a bijel mass transfer apparatus fabricated by 3d-printing of bijel fibers and soft photolithography will be introduced. In conjunction with the following objective, the analysis of convective flows in bijels will facilitate a thorough description of their structure/function relationships.
(c) Biphasic chemical reactions in STrIPS bijel cross-flow reactors. First, continuous extraction in bijels will be realized. Next, conditions to carry out continuously-operated, phase transfer catalysis of well-known model reactions in bijels will be determined. Both processes will be characterized in-situ and in 3-dimensions by confocal microscopy of fluorescent phase transfer reactions in transparent bijels.
Max ERC Funding
1 905 000 €
Duration
Start date: 2019-06-01, End date: 2024-05-31
Project acronym 3D-REPAIR
Project Spatial organization of DNA repair within the nucleus
Researcher (PI) Evanthia Soutoglou
Host Institution (HI) CENTRE EUROPEEN DE RECHERCHE EN BIOLOGIE ET MEDECINE
Call Details Consolidator Grant (CoG), LS2, ERC-2015-CoG
Summary Faithful repair of double stranded DNA breaks (DSBs) is essential, as they are at the origin of genome instability, chromosomal translocations and cancer. Cells repair DSBs through different pathways, which can be faithful or mutagenic, and the balance between them at a given locus must be tightly regulated to preserve genome integrity. Although, much is known about DSB repair factors, how the choice between pathways is controlled within the nuclear environment is not understood. We have shown that nuclear architecture and non-random genome organization determine the frequency of chromosomal translocations and that pathway choice is dictated by the spatial organization of DNA in the nucleus. Nevertheless, what determines which pathway is activated in response to DSBs at specific genomic locations is not understood. Furthermore, the impact of 3D-genome folding on the kinetics and efficiency of DSB repair is completely unknown.
Here we aim to understand how nuclear compartmentalization, chromatin structure and genome organization impact on the efficiency of detection, signaling and repair of DSBs. We will unravel what determines the DNA repair specificity within distinct nuclear compartments using protein tethering, promiscuous biotinylation and quantitative proteomics. We will determine how DNA repair is orchestrated at different heterochromatin structures using a CRISPR/Cas9-based system that allows, for the first time robust induction of DSBs at specific heterochromatin compartments. Finally, we will investigate the role of 3D-genome folding in the kinetics of DNA repair and pathway choice using single nucleotide resolution DSB-mapping coupled to 3D-topological maps.
This proposal has significant implications for understanding the mechanisms controlling DNA repair within the nuclear environment and will reveal the regions of the genome that are susceptible to genomic instability and help us understand why certain mutations and translocations are recurrent in cancer
Summary
Faithful repair of double stranded DNA breaks (DSBs) is essential, as they are at the origin of genome instability, chromosomal translocations and cancer. Cells repair DSBs through different pathways, which can be faithful or mutagenic, and the balance between them at a given locus must be tightly regulated to preserve genome integrity. Although, much is known about DSB repair factors, how the choice between pathways is controlled within the nuclear environment is not understood. We have shown that nuclear architecture and non-random genome organization determine the frequency of chromosomal translocations and that pathway choice is dictated by the spatial organization of DNA in the nucleus. Nevertheless, what determines which pathway is activated in response to DSBs at specific genomic locations is not understood. Furthermore, the impact of 3D-genome folding on the kinetics and efficiency of DSB repair is completely unknown.
Here we aim to understand how nuclear compartmentalization, chromatin structure and genome organization impact on the efficiency of detection, signaling and repair of DSBs. We will unravel what determines the DNA repair specificity within distinct nuclear compartments using protein tethering, promiscuous biotinylation and quantitative proteomics. We will determine how DNA repair is orchestrated at different heterochromatin structures using a CRISPR/Cas9-based system that allows, for the first time robust induction of DSBs at specific heterochromatin compartments. Finally, we will investigate the role of 3D-genome folding in the kinetics of DNA repair and pathway choice using single nucleotide resolution DSB-mapping coupled to 3D-topological maps.
This proposal has significant implications for understanding the mechanisms controlling DNA repair within the nuclear environment and will reveal the regions of the genome that are susceptible to genomic instability and help us understand why certain mutations and translocations are recurrent in cancer
Max ERC Funding
1 999 750 €
Duration
Start date: 2017-03-01, End date: 2022-02-28
Project acronym 3D2DPrint
Project 3D Printing of Novel 2D Nanomaterials: Adding Advanced 2D Functionalities to Revolutionary Tailored 3D Manufacturing
Researcher (PI) Valeria Nicolosi
Host Institution (HI) THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN
Call Details Consolidator Grant (CoG), PE8, ERC-2015-CoG
Summary My vision is to establish, within the framework of an ERC CoG, a multidisciplinary group which will work in concert towards pioneering the integration of novel 2-Dimensional nanomaterials with novel additive fabrication techniques to develop a unique class of energy storage devices.
Batteries and supercapacitors are two very complementary types of energy storage devices. Batteries store much higher energy densities; supercapacitors, on the other hand, hold one tenth of the electricity per unit of volume or weight as compared to batteries but can achieve much higher power densities. Technology is currently striving to improve the power density of batteries and the energy density of supercapacitors. To do so it is imperative to develop new materials, chemistries and manufacturing strategies.
3D2DPrint aims to develop micro-energy devices (both supercapacitors and batteries), technologies particularly relevant in the context of the emergent industry of micro-electro-mechanical systems and constantly downsized electronics. We plan to use novel two-dimensional (2D) nanomaterials obtained by liquid-phase exfoliation. This method offers a new, economic and easy way to prepare ink of a variety of 2D systems, allowing to produce wide device performance window through elegant and simple constituent control at the point of fabrication. 3D2DPrint will use our expertise and know-how to allow development of advanced AM methods to integrate dissimilar nanomaterial blends and/or “hybrids” into fully embedded 3D printed energy storage devices, with the ultimate objective to realise a range of products that contain the above described nanomaterials subcomponent devices, electrical connections and traditional micro-fabricated subcomponents (if needed) ideally using a single tool.
Summary
My vision is to establish, within the framework of an ERC CoG, a multidisciplinary group which will work in concert towards pioneering the integration of novel 2-Dimensional nanomaterials with novel additive fabrication techniques to develop a unique class of energy storage devices.
Batteries and supercapacitors are two very complementary types of energy storage devices. Batteries store much higher energy densities; supercapacitors, on the other hand, hold one tenth of the electricity per unit of volume or weight as compared to batteries but can achieve much higher power densities. Technology is currently striving to improve the power density of batteries and the energy density of supercapacitors. To do so it is imperative to develop new materials, chemistries and manufacturing strategies.
3D2DPrint aims to develop micro-energy devices (both supercapacitors and batteries), technologies particularly relevant in the context of the emergent industry of micro-electro-mechanical systems and constantly downsized electronics. We plan to use novel two-dimensional (2D) nanomaterials obtained by liquid-phase exfoliation. This method offers a new, economic and easy way to prepare ink of a variety of 2D systems, allowing to produce wide device performance window through elegant and simple constituent control at the point of fabrication. 3D2DPrint will use our expertise and know-how to allow development of advanced AM methods to integrate dissimilar nanomaterial blends and/or “hybrids” into fully embedded 3D printed energy storage devices, with the ultimate objective to realise a range of products that contain the above described nanomaterials subcomponent devices, electrical connections and traditional micro-fabricated subcomponents (if needed) ideally using a single tool.
Max ERC Funding
2 499 942 €
Duration
Start date: 2016-10-01, End date: 2021-09-30
Project acronym 3DAddChip
Project Additive manufacturing of 2D nanomaterials for on-chip technologies
Researcher (PI) Cecilia Mattevi
Host Institution (HI) IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Call Details Consolidator Grant (CoG), PE8, ERC-2018-COG
Summary The realization of “the internet of things” is inevitably constrained at the level of miniaturization that can be achieved in the electronic devices. A variety of technologies are now going through a process of miniaturization from micro-electromechanical systems (MEMS) to biomedical sensors, and actuators. The ultimate goal is to combine several components in an individual multifunctional platform, realizing on-chip technology. Devices have to be constrained to small footprints and exhibit high performance. Thus, the miniaturization process requires the introduction of new manufacturing processes to fabricate devices in the 3D space over small areas. 3D printing via robocasting is emerging as a new manufacturing technique, which allows shaping virtually any materials from polymers to ceramic and metals into complex architectures.
The goal of this research is to establish a 3D printing paradigm to produce miniaturized complex shape devices with diversified functions for on-chip technologies adaptable to “smart environment” such as flexible substrates, smart textiles and biomedical sensors. The elementary building blocks of the devices will be two-dimensional nanomaterials, which present unique optical, electrical, chemical and mechanical properties. The synergistic combination of the intrinsic characteristics of the 2D nanomaterials and the specific 3D architecture will enable advanced performance of the 3D printed objects. This research programme will demonstrate 3D miniaturized energy storage and energy conversion units fabricated with inks produced using a pilot plant. These units are essential components of any on-chip platform as they ensure energy autonomy via self-powering. Ultimately, this research will initiate new technologies based on miniaturized 3D devices.
Summary
The realization of “the internet of things” is inevitably constrained at the level of miniaturization that can be achieved in the electronic devices. A variety of technologies are now going through a process of miniaturization from micro-electromechanical systems (MEMS) to biomedical sensors, and actuators. The ultimate goal is to combine several components in an individual multifunctional platform, realizing on-chip technology. Devices have to be constrained to small footprints and exhibit high performance. Thus, the miniaturization process requires the introduction of new manufacturing processes to fabricate devices in the 3D space over small areas. 3D printing via robocasting is emerging as a new manufacturing technique, which allows shaping virtually any materials from polymers to ceramic and metals into complex architectures.
The goal of this research is to establish a 3D printing paradigm to produce miniaturized complex shape devices with diversified functions for on-chip technologies adaptable to “smart environment” such as flexible substrates, smart textiles and biomedical sensors. The elementary building blocks of the devices will be two-dimensional nanomaterials, which present unique optical, electrical, chemical and mechanical properties. The synergistic combination of the intrinsic characteristics of the 2D nanomaterials and the specific 3D architecture will enable advanced performance of the 3D printed objects. This research programme will demonstrate 3D miniaturized energy storage and energy conversion units fabricated with inks produced using a pilot plant. These units are essential components of any on-chip platform as they ensure energy autonomy via self-powering. Ultimately, this research will initiate new technologies based on miniaturized 3D devices.
Max ERC Funding
1 999 968 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
Project acronym 4C
Project 4C technology: uncovering the multi-dimensional structure of the genome
Researcher (PI) Wouter Leonard De Laat
Host Institution (HI) KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW
Call Details Starting Grant (StG), LS2, ERC-2007-StG
Summary The architecture of DNA in the cell nucleus is an emerging epigenetic key contributor to genome function. We recently developed 4C technology, a high-throughput technique that combines state-of-the-art 3C technology with tailored micro-arrays to uniquely allow for an unbiased genome-wide search for DNA loci that interact in the nuclear space. Based on 4C technology, we were the first to provide a comprehensive overview of long-range DNA contacts of selected loci. The data showed that active and inactive chromatin domains contact many distinct regions within and between chromosomes and genes switch long-range DNA contacts in relation to their expression status. 4C technology not only allows investigating the three-dimensional structure of DNA in the nucleus, it also accurately reconstructs at least 10 megabases of the one-dimensional chromosome sequence map around the target sequence. Changes in this physical map as a result of genomic rearrangements are therefore identified by 4C technology. We recently demonstrated that 4C detects deletions, balanced inversions and translocations in patient samples at a resolution (~7kb) that allowed immediate sequencing of the breakpoints. Excitingly, 4C technology therefore offers the first high-resolution genomic approach that can identify both balanced and unbalanced genomic rearrangements. 4C is expected to become an important tool in clinical diagnosis and prognosis. Key objectives of this proposal are: 1. Explore the functional significance of DNA folding in the nucleus by systematically applying 4C technology to differentially expressed gene loci. 2. Adapt 4C technology such that it allows for massive parallel analysis of DNA interactions between regulatory elements and gene promoters. This method would greatly facilitate the identification of functionally relevant DNA elements in the genome. 3. Develop 4C technology into a clinical diagnostic tool for the accurate detection of balanced and unbalanced rearrangements.
Summary
The architecture of DNA in the cell nucleus is an emerging epigenetic key contributor to genome function. We recently developed 4C technology, a high-throughput technique that combines state-of-the-art 3C technology with tailored micro-arrays to uniquely allow for an unbiased genome-wide search for DNA loci that interact in the nuclear space. Based on 4C technology, we were the first to provide a comprehensive overview of long-range DNA contacts of selected loci. The data showed that active and inactive chromatin domains contact many distinct regions within and between chromosomes and genes switch long-range DNA contacts in relation to their expression status. 4C technology not only allows investigating the three-dimensional structure of DNA in the nucleus, it also accurately reconstructs at least 10 megabases of the one-dimensional chromosome sequence map around the target sequence. Changes in this physical map as a result of genomic rearrangements are therefore identified by 4C technology. We recently demonstrated that 4C detects deletions, balanced inversions and translocations in patient samples at a resolution (~7kb) that allowed immediate sequencing of the breakpoints. Excitingly, 4C technology therefore offers the first high-resolution genomic approach that can identify both balanced and unbalanced genomic rearrangements. 4C is expected to become an important tool in clinical diagnosis and prognosis. Key objectives of this proposal are: 1. Explore the functional significance of DNA folding in the nucleus by systematically applying 4C technology to differentially expressed gene loci. 2. Adapt 4C technology such that it allows for massive parallel analysis of DNA interactions between regulatory elements and gene promoters. This method would greatly facilitate the identification of functionally relevant DNA elements in the genome. 3. Develop 4C technology into a clinical diagnostic tool for the accurate detection of balanced and unbalanced rearrangements.
Max ERC Funding
1 225 000 €
Duration
Start date: 2008-09-01, End date: 2013-08-31
Project acronym AArteMIS
Project Aneurysmal Arterial Mechanics: Into the Structure
Researcher (PI) Pierre Joseph Badel
Host Institution (HI) ASSOCIATION POUR LA RECHERCHE ET LE DEVELOPPEMENT DES METHODES ET PROCESSUS INDUSTRIELS
Call Details Starting Grant (StG), PE8, ERC-2014-STG
Summary The rupture of an Aortic Aneurysm (AA), which is often lethal, is a mechanical phenomenon that occurs when the wall stress state exceeds the local strength of the tissue. Our current understanding of arterial rupture mechanisms is poor, and the physics taking place at the microscopic scale in these collagenous structures remains an open area of research. Understanding, modelling, and quantifying the micro-mechanisms which drive the mechanical response of such tissue and locally trigger rupture represents the most challenging and promising pathway towards predictive diagnosis and personalized care of AA.
The PI's group was recently able to detect, in advance, at the macro-scale, rupture-prone areas in bulging arterial tissues. The next step is to get into the details of the arterial microstructure to elucidate the underlying mechanisms.
Through the achievements of AArteMIS, the local mechanical state of the fibrous microstructure of the tissue, especially close to its rupture state, will be quantitatively analyzed from multi-photon confocal microscopy and numerically reconstructed to establish quantitative micro-scale rupture criteria. AArteMIS will also address developing micro-macro models which are based on the collected quantitative data.
The entire project will be completed through collaboration with medical doctors and engineers, experts in all required fields for the success of AArteMIS.
AArteMIS is expected to open longed-for pathways for research in soft tissue mechanobiology which focuses on cell environment and to enable essential clinical applications for the quantitative assessment of AA rupture risk. It will significantly contribute to understanding fatal vascular events and improving cardiovascular treatments. It will provide a tremendous source of data and inspiration for subsequent applications and research by answering the most fundamental questions on AA rupture behaviour enabling ground-breaking clinical changes to take place.
Summary
The rupture of an Aortic Aneurysm (AA), which is often lethal, is a mechanical phenomenon that occurs when the wall stress state exceeds the local strength of the tissue. Our current understanding of arterial rupture mechanisms is poor, and the physics taking place at the microscopic scale in these collagenous structures remains an open area of research. Understanding, modelling, and quantifying the micro-mechanisms which drive the mechanical response of such tissue and locally trigger rupture represents the most challenging and promising pathway towards predictive diagnosis and personalized care of AA.
The PI's group was recently able to detect, in advance, at the macro-scale, rupture-prone areas in bulging arterial tissues. The next step is to get into the details of the arterial microstructure to elucidate the underlying mechanisms.
Through the achievements of AArteMIS, the local mechanical state of the fibrous microstructure of the tissue, especially close to its rupture state, will be quantitatively analyzed from multi-photon confocal microscopy and numerically reconstructed to establish quantitative micro-scale rupture criteria. AArteMIS will also address developing micro-macro models which are based on the collected quantitative data.
The entire project will be completed through collaboration with medical doctors and engineers, experts in all required fields for the success of AArteMIS.
AArteMIS is expected to open longed-for pathways for research in soft tissue mechanobiology which focuses on cell environment and to enable essential clinical applications for the quantitative assessment of AA rupture risk. It will significantly contribute to understanding fatal vascular events and improving cardiovascular treatments. It will provide a tremendous source of data and inspiration for subsequent applications and research by answering the most fundamental questions on AA rupture behaviour enabling ground-breaking clinical changes to take place.
Max ERC Funding
1 499 783 €
Duration
Start date: 2015-04-01, End date: 2020-03-31
Project acronym ABEP
Project Asset Bubbles and Economic Policy
Researcher (PI) Jaume Ventura Fontanet
Host Institution (HI) Centre de Recerca en Economia Internacional (CREI)
Call Details Advanced Grant (AdG), SH1, ERC-2009-AdG
Summary Advanced capitalist economies experience large and persistent movements in asset prices that are difficult to justify with economic fundamentals. The internet bubble of the 1990s and the real state market bubble of the 2000s are two recent examples. The predominant view is that these bubbles are a market failure, and are caused by some form of individual irrationality on the part of market participants. This project is based instead on the view that market participants are individually rational, although this does not preclude sometimes collectively sub-optimal outcomes. Bubbles are thus not a source of market failure by themselves but instead arise as a result of a pre-existing market failure, namely, the existence of pockets of dynamically inefficient investments. Under some conditions, bubbles partly solve this problem, increasing market efficiency and welfare. It is also possible however that bubbles do not solve the underlying problem and, in addition, create negative side-effects. The main objective of this project is to develop this view of asset bubbles, and produce an empirically-relevant macroeconomic framework that allows us to address the following questions: (i) What is the relationship between bubbles and financial market frictions? Special emphasis is given to how the globalization of financial markets and the development of new financial products affect the size and effects of bubbles. (ii) What is the relationship between bubbles, economic growth and unemployment? The theory suggests the presence of virtuous and vicious cycles, as economic growth creates the conditions for bubbles to pop up, while bubbles create incentives for economic growth to happen. (iii) What is the optimal policy to manage bubbles? We need to develop the tools that allow policy makers to sustain those bubbles that have positive effects and burst those that have negative effects.
Summary
Advanced capitalist economies experience large and persistent movements in asset prices that are difficult to justify with economic fundamentals. The internet bubble of the 1990s and the real state market bubble of the 2000s are two recent examples. The predominant view is that these bubbles are a market failure, and are caused by some form of individual irrationality on the part of market participants. This project is based instead on the view that market participants are individually rational, although this does not preclude sometimes collectively sub-optimal outcomes. Bubbles are thus not a source of market failure by themselves but instead arise as a result of a pre-existing market failure, namely, the existence of pockets of dynamically inefficient investments. Under some conditions, bubbles partly solve this problem, increasing market efficiency and welfare. It is also possible however that bubbles do not solve the underlying problem and, in addition, create negative side-effects. The main objective of this project is to develop this view of asset bubbles, and produce an empirically-relevant macroeconomic framework that allows us to address the following questions: (i) What is the relationship between bubbles and financial market frictions? Special emphasis is given to how the globalization of financial markets and the development of new financial products affect the size and effects of bubbles. (ii) What is the relationship between bubbles, economic growth and unemployment? The theory suggests the presence of virtuous and vicious cycles, as economic growth creates the conditions for bubbles to pop up, while bubbles create incentives for economic growth to happen. (iii) What is the optimal policy to manage bubbles? We need to develop the tools that allow policy makers to sustain those bubbles that have positive effects and burst those that have negative effects.
Max ERC Funding
1 000 000 €
Duration
Start date: 2010-04-01, End date: 2015-03-31
Project acronym ABRSEIST
Project Antibiotic Resistance: Socio-Economic Determinants and the Role of Information and Salience in Treatment Choice
Researcher (PI) Hannes ULLRICH
Host Institution (HI) DEUTSCHES INSTITUT FUR WIRTSCHAFTSFORSCHUNG DIW (INSTITUT FUR KONJUNKTURFORSCHUNG) EV
Call Details Starting Grant (StG), SH1, ERC-2018-STG
Summary Antibiotics have contributed to a tremendous increase in human well-being, saving many millions of lives. However, antibiotics become obsolete the more they are used as selection pressure promotes the development of resistant bacteria. The World Health Organization has proclaimed antibiotic resistance as a major global threat to public health. Today, 700,000 deaths per year are due to untreatable infections. To win the battle against antibiotic resistance, new policies affecting the supply and demand of existing and new drugs must be designed. I propose new research to identify and evaluate feasible and effective demand-side policy interventions targeting the relevant decision makers: physicians and patients. ABRSEIST will make use of a broad econometric toolset to identify mechanisms linking antibiotic resistance and consumption exploiting a unique combination of physician-patient-level antibiotic resistance, treatment, and socio-economic data. Using machine learning methods adapted for causal inference, theory-driven structural econometric analysis, and randomization in the field it will provide rigorous evidence on effective intervention designs. This research will improve our understanding of how prescribing, resistance, and the effect of antibiotic use on resistance, are distributed in the general population which has important implications for the design of targeted interventions. It will then estimate a structural model of general practitioners’ acquisition and use of information under uncertainty about resistance in prescription choice, allowing counterfactual analysis of information-improving policies such as mandatory diagnostic testing. The large-scale and structural econometric analyses allow flexible identification of physician heterogeneity, which ABRSEIST will exploit to design and evaluate targeted, randomized information nudges in the field. The result will be improved rational use and a toolset applicable in contexts of antibiotic prescribing.
Summary
Antibiotics have contributed to a tremendous increase in human well-being, saving many millions of lives. However, antibiotics become obsolete the more they are used as selection pressure promotes the development of resistant bacteria. The World Health Organization has proclaimed antibiotic resistance as a major global threat to public health. Today, 700,000 deaths per year are due to untreatable infections. To win the battle against antibiotic resistance, new policies affecting the supply and demand of existing and new drugs must be designed. I propose new research to identify and evaluate feasible and effective demand-side policy interventions targeting the relevant decision makers: physicians and patients. ABRSEIST will make use of a broad econometric toolset to identify mechanisms linking antibiotic resistance and consumption exploiting a unique combination of physician-patient-level antibiotic resistance, treatment, and socio-economic data. Using machine learning methods adapted for causal inference, theory-driven structural econometric analysis, and randomization in the field it will provide rigorous evidence on effective intervention designs. This research will improve our understanding of how prescribing, resistance, and the effect of antibiotic use on resistance, are distributed in the general population which has important implications for the design of targeted interventions. It will then estimate a structural model of general practitioners’ acquisition and use of information under uncertainty about resistance in prescription choice, allowing counterfactual analysis of information-improving policies such as mandatory diagnostic testing. The large-scale and structural econometric analyses allow flexible identification of physician heterogeneity, which ABRSEIST will exploit to design and evaluate targeted, randomized information nudges in the field. The result will be improved rational use and a toolset applicable in contexts of antibiotic prescribing.
Max ERC Funding
1 498 920 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym ACAP
Project Acency Costs and Asset Pricing
Researcher (PI) Thomas Mariotti
Host Institution (HI) FONDATION JEAN-JACQUES LAFFONT,TOULOUSE SCIENCES ECONOMIQUES
Call Details Starting Grant (StG), SH1, ERC-2007-StG
Summary The main objective of this research project is to contribute at bridging the gap between the two main branches of financial theory, namely corporate finance and asset pricing. It is motivated by the conviction that these two aspects of financial activity should and can be analyzed within a unified framework. This research will borrow from these two approaches in order to construct theoretical models that allow one to analyze the design and issuance of financial securities, as well as the dynamics of their valuations. Unlike asset pricing, which takes as given the price of the fundamentals, the goal is to derive security price processes from a precise description of firm’s operations and internal frictions. Regarding the latter, and in line with traditional corporate finance theory, the analysis will emphasize the role of agency costs within the firm for the design of its securities. But the analysis will be pushed one step further by studying the impact of these agency costs on key financial variables such as stock and bond prices, leverage, book-to-market ratios, default risk, or the holding of liquidities by firms. One of the contributions of this research project is to show how these variables are interrelated when firms and investors agree upon optimal financial arrangements. The final objective is to derive a rich set of testable asset pricing implications that would eventually be brought to the data.
Summary
The main objective of this research project is to contribute at bridging the gap between the two main branches of financial theory, namely corporate finance and asset pricing. It is motivated by the conviction that these two aspects of financial activity should and can be analyzed within a unified framework. This research will borrow from these two approaches in order to construct theoretical models that allow one to analyze the design and issuance of financial securities, as well as the dynamics of their valuations. Unlike asset pricing, which takes as given the price of the fundamentals, the goal is to derive security price processes from a precise description of firm’s operations and internal frictions. Regarding the latter, and in line with traditional corporate finance theory, the analysis will emphasize the role of agency costs within the firm for the design of its securities. But the analysis will be pushed one step further by studying the impact of these agency costs on key financial variables such as stock and bond prices, leverage, book-to-market ratios, default risk, or the holding of liquidities by firms. One of the contributions of this research project is to show how these variables are interrelated when firms and investors agree upon optimal financial arrangements. The final objective is to derive a rich set of testable asset pricing implications that would eventually be brought to the data.
Max ERC Funding
1 000 000 €
Duration
Start date: 2008-11-01, End date: 2014-10-31
Project acronym ACCOMPLI
Project Assembly and maintenance of a co-regulated chromosomal compartment
Researcher (PI) Peter Burkhard Becker
Host Institution (HI) LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Call Details Advanced Grant (AdG), LS2, ERC-2011-ADG_20110310
Summary "Eukaryotic nuclei are organised into functional compartments, – local microenvironments that are enriched in certain molecules or biochemical activities and therefore specify localised functional outputs. Our study seeks to unveil fundamental principles of co-regulation of genes in a chromo¬somal compartment and the preconditions for homeostasis of such a compartment in the dynamic nuclear environment.
The dosage-compensated X chromosome of male Drosophila flies satisfies the criteria for a functional com¬partment. It is rendered structurally distinct from all other chromosomes by association of a regulatory ribonucleoprotein ‘Dosage Compensation Complex’ (DCC), enrichment of histone modifications and global decondensation. As a result, most genes on the X chromosome are co-ordinately activated. Autosomal genes inserted into the X acquire X-chromosomal features and are subject to the X-specific regulation.
We seek to uncover the molecular principles that initiate, establish and maintain the dosage-compensated chromosome. We will follow the kinetics of DCC assembly and the timing of association with different types of chromosomal targets in nuclei with high spatial resolution afforded by sub-wavelength microscopy and deep sequencing of DNA binding sites. We will characterise DCC sub-complexes with respect to their roles as kinetic assembly intermediates or as representations of local, functional heterogeneity. We will evaluate the roles of a DCC- novel ubiquitin ligase activity for homeostasis.
Crucial to the recruitment of the DCC and its distribution to target genes are non-coding roX RNAs that are transcribed from the X. We will determine the secondary structure ‘signatures’ of roX RNAs in vitro and determine the binding sites of the protein subunits in vivo. By biochemical and cellular reconstitution will test the hypothesis that roX-encoded RNA aptamers orchestrate the assembly of the DCC and contribute to the exquisite targeting of the complex."
Summary
"Eukaryotic nuclei are organised into functional compartments, – local microenvironments that are enriched in certain molecules or biochemical activities and therefore specify localised functional outputs. Our study seeks to unveil fundamental principles of co-regulation of genes in a chromo¬somal compartment and the preconditions for homeostasis of such a compartment in the dynamic nuclear environment.
The dosage-compensated X chromosome of male Drosophila flies satisfies the criteria for a functional com¬partment. It is rendered structurally distinct from all other chromosomes by association of a regulatory ribonucleoprotein ‘Dosage Compensation Complex’ (DCC), enrichment of histone modifications and global decondensation. As a result, most genes on the X chromosome are co-ordinately activated. Autosomal genes inserted into the X acquire X-chromosomal features and are subject to the X-specific regulation.
We seek to uncover the molecular principles that initiate, establish and maintain the dosage-compensated chromosome. We will follow the kinetics of DCC assembly and the timing of association with different types of chromosomal targets in nuclei with high spatial resolution afforded by sub-wavelength microscopy and deep sequencing of DNA binding sites. We will characterise DCC sub-complexes with respect to their roles as kinetic assembly intermediates or as representations of local, functional heterogeneity. We will evaluate the roles of a DCC- novel ubiquitin ligase activity for homeostasis.
Crucial to the recruitment of the DCC and its distribution to target genes are non-coding roX RNAs that are transcribed from the X. We will determine the secondary structure ‘signatures’ of roX RNAs in vitro and determine the binding sites of the protein subunits in vivo. By biochemical and cellular reconstitution will test the hypothesis that roX-encoded RNA aptamers orchestrate the assembly of the DCC and contribute to the exquisite targeting of the complex."
Max ERC Funding
2 482 770 €
Duration
Start date: 2012-02-01, End date: 2017-01-31
Project acronym ACOULOMODE
Project Advanced coupling of low order combustor simulations with thermoacoustic modelling and controller design
Researcher (PI) Aimee Morgans
Host Institution (HI) IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Call Details Starting Grant (StG), PE8, ERC-2012-StG_20111012
Summary "Combustion is essential to the world’s energy generation and transport needs, and will remain so for the foreseeable future. Mitigating its impact on the climate and human health, by reducing its associated emissions, is thus a priority. One significant challenge for gas-turbine combustion is combustion instability, which is currently inhibiting reductions in NOx emissions (these damage human health via a deterioration in air quality). Combustion instability is caused by a two-way coupling between unsteady combustion and acoustic waves - the large pressure oscillations that result can cause substantial mechanical damage. Currently, the lack of fast, accurate modelling tools for combustion instability, and the lack of reliable ways of suppressing it are severely hindering reductions in NOx emissions.
This proposal aims to make step improvements in both fast, accurate modelling of combustion instability, and in developing reliable active control strategies for its suppression. It will achieve this by coupling low order combustor models (these are fast, simplified models for simulating combustion instability) with advances in analytical modelling, CFD simulation, reduced order modelling and control theory tools. In particular:
* important advances in accurately incorporating the effect of entropy waves (temperature variations resulting from unsteady combustion) and non-linear flame models will be made;
* new active control strategies for achieving reliable suppression of combustion instability, including from within limit cycle oscillations, will be developed;
* an open-source low order combustor modelling tool will be developed and widely disseminated, opening access to researchers worldwide and improving communications between the fields of thermoacoustics and control theory.
Thus the proposal aims to use analytical and computational methods to contribute to achieving low NOx gas-turbine combustion, without the penalty of damaging combustion instability."
Summary
"Combustion is essential to the world’s energy generation and transport needs, and will remain so for the foreseeable future. Mitigating its impact on the climate and human health, by reducing its associated emissions, is thus a priority. One significant challenge for gas-turbine combustion is combustion instability, which is currently inhibiting reductions in NOx emissions (these damage human health via a deterioration in air quality). Combustion instability is caused by a two-way coupling between unsteady combustion and acoustic waves - the large pressure oscillations that result can cause substantial mechanical damage. Currently, the lack of fast, accurate modelling tools for combustion instability, and the lack of reliable ways of suppressing it are severely hindering reductions in NOx emissions.
This proposal aims to make step improvements in both fast, accurate modelling of combustion instability, and in developing reliable active control strategies for its suppression. It will achieve this by coupling low order combustor models (these are fast, simplified models for simulating combustion instability) with advances in analytical modelling, CFD simulation, reduced order modelling and control theory tools. In particular:
* important advances in accurately incorporating the effect of entropy waves (temperature variations resulting from unsteady combustion) and non-linear flame models will be made;
* new active control strategies for achieving reliable suppression of combustion instability, including from within limit cycle oscillations, will be developed;
* an open-source low order combustor modelling tool will be developed and widely disseminated, opening access to researchers worldwide and improving communications between the fields of thermoacoustics and control theory.
Thus the proposal aims to use analytical and computational methods to contribute to achieving low NOx gas-turbine combustion, without the penalty of damaging combustion instability."
Max ERC Funding
1 489 309 €
Duration
Start date: 2013-01-01, End date: 2017-12-31
Project acronym ACTIVATION OF XCI
Project Molecular mechanisms controlling X chromosome inactivation
Researcher (PI) Joost Henk Gribnau
Host Institution (HI) ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM
Call Details Starting Grant (StG), LS2, ERC-2010-StG_20091118
Summary In mammals, gene dosage of X-chromosomal genes is equalized between sexes by random inactivation of either one of the two X chromosomes in female cells. In the initial phase of X chromosome inactivation (XCI), a counting and initiation process determines the number of X chromosomes per nucleus, and elects the future inactive X chromosome (Xi). Xist is an X-encoded gene that plays a crucial role in the XCI process. At the start of XCI Xist expression is up-regulated and Xist RNA accumulates on the future Xi thereby initiating silencing in cis. Recent work performed in my laboratory indicates that the counting and initiation process is directed by a stochastic mechanism, in which each X chromosome has an independent probability to be inactivated. We also found that this probability is determined by the X:ploïdy ratio. These results indicated the presence of at least one X-linked activator of XCI. With a BAC screen we recently identified X-encoded RNF12 to be a dose-dependent activator of XCI. Expression of RNF12 correlates with Xist expression, and a heterozygous deletion of Rnf12 results in a marked loss of XCI in female cells. The presence of a small proportion of cells that still initiate XCI, in Rnf12+/- cells, also indicated that more XCI-activators are involved in XCI. Here, we propose to investigate the molecular mechanism by which RNF12 activates XCI in mouse and human, and to search for additional XCI-activators. We will also attempt to establish the role of different inhibitors of XCI, including CTCF and the pluripotency factors OCT4, SOX2 and NANOG. We anticipate that these studies will significantly advance our understanding of XCI mechanisms, which is highly relevant for a better insight in the manifestation of X-linked diseases that are affected by XCI.
Summary
In mammals, gene dosage of X-chromosomal genes is equalized between sexes by random inactivation of either one of the two X chromosomes in female cells. In the initial phase of X chromosome inactivation (XCI), a counting and initiation process determines the number of X chromosomes per nucleus, and elects the future inactive X chromosome (Xi). Xist is an X-encoded gene that plays a crucial role in the XCI process. At the start of XCI Xist expression is up-regulated and Xist RNA accumulates on the future Xi thereby initiating silencing in cis. Recent work performed in my laboratory indicates that the counting and initiation process is directed by a stochastic mechanism, in which each X chromosome has an independent probability to be inactivated. We also found that this probability is determined by the X:ploïdy ratio. These results indicated the presence of at least one X-linked activator of XCI. With a BAC screen we recently identified X-encoded RNF12 to be a dose-dependent activator of XCI. Expression of RNF12 correlates with Xist expression, and a heterozygous deletion of Rnf12 results in a marked loss of XCI in female cells. The presence of a small proportion of cells that still initiate XCI, in Rnf12+/- cells, also indicated that more XCI-activators are involved in XCI. Here, we propose to investigate the molecular mechanism by which RNF12 activates XCI in mouse and human, and to search for additional XCI-activators. We will also attempt to establish the role of different inhibitors of XCI, including CTCF and the pluripotency factors OCT4, SOX2 and NANOG. We anticipate that these studies will significantly advance our understanding of XCI mechanisms, which is highly relevant for a better insight in the manifestation of X-linked diseases that are affected by XCI.
Max ERC Funding
1 500 000 €
Duration
Start date: 2011-04-01, End date: 2016-03-31
Project acronym ActiveWindFarms
Project Active Wind Farms: Optimization and Control of Atmospheric Energy Extraction in Gigawatt Wind Farms
Researcher (PI) Johan Meyers
Host Institution (HI) KATHOLIEKE UNIVERSITEIT LEUVEN
Call Details Starting Grant (StG), PE8, ERC-2012-StG_20111012
Summary With the recognition that wind energy will become an important contributor to the world’s energy portfolio, several wind farms with a capacity of over 1 gigawatt are in planning phase. In the past, engineering of wind farms focused on a bottom-up approach, in which atmospheric wind availability was considered to be fixed by climate and weather. However, farms of gigawatt size slow down the Atmospheric Boundary Layer (ABL) as a whole, reducing the availability of wind at turbine hub height. In Denmark’s large off-shore farms, this leads to underperformance of turbines which can reach levels of 40%–50% compared to the same turbine in a lone-standing case. For large wind farms, the vertical structure and turbulence physics of the flow in the ABL become crucial ingredients in their design and operation. This introduces a new set of scientific challenges related to the design and control of large wind farms. The major ambition of the present research proposal is to employ optimal control techniques to control the interaction between large wind farms and the ABL, and optimize overall farm-power extraction. Individual turbines are used as flow actuators by dynamically pitching their blades using time scales ranging between 10 to 500 seconds. The application of such control efforts on the atmospheric boundary layer has never been attempted before, and introduces flow control on a physical scale which is currently unprecedented. The PI possesses a unique combination of expertise and tools enabling these developments: efficient parallel large-eddy simulations of wind farms, multi-scale turbine modeling, and gradient-based optimization in large optimization-parameter spaces using adjoint formulations. To ensure a maximum impact on the wind-engineering field, the project aims at optimal control, experimental wind-tunnel validation, and at including multi-disciplinary aspects, related to structural mechanics, power quality, and controller design.
Summary
With the recognition that wind energy will become an important contributor to the world’s energy portfolio, several wind farms with a capacity of over 1 gigawatt are in planning phase. In the past, engineering of wind farms focused on a bottom-up approach, in which atmospheric wind availability was considered to be fixed by climate and weather. However, farms of gigawatt size slow down the Atmospheric Boundary Layer (ABL) as a whole, reducing the availability of wind at turbine hub height. In Denmark’s large off-shore farms, this leads to underperformance of turbines which can reach levels of 40%–50% compared to the same turbine in a lone-standing case. For large wind farms, the vertical structure and turbulence physics of the flow in the ABL become crucial ingredients in their design and operation. This introduces a new set of scientific challenges related to the design and control of large wind farms. The major ambition of the present research proposal is to employ optimal control techniques to control the interaction between large wind farms and the ABL, and optimize overall farm-power extraction. Individual turbines are used as flow actuators by dynamically pitching their blades using time scales ranging between 10 to 500 seconds. The application of such control efforts on the atmospheric boundary layer has never been attempted before, and introduces flow control on a physical scale which is currently unprecedented. The PI possesses a unique combination of expertise and tools enabling these developments: efficient parallel large-eddy simulations of wind farms, multi-scale turbine modeling, and gradient-based optimization in large optimization-parameter spaces using adjoint formulations. To ensure a maximum impact on the wind-engineering field, the project aims at optimal control, experimental wind-tunnel validation, and at including multi-disciplinary aspects, related to structural mechanics, power quality, and controller design.
Max ERC Funding
1 499 241 €
Duration
Start date: 2012-10-01, End date: 2017-09-30
Project acronym AEROFLEX
Project AEROelastic instabilities and control of FLEXible Structures
Researcher (PI) Olivier Pierre MARQUET
Host Institution (HI) OFFICE NATIONAL D'ETUDES ET DE RECHERCHES AEROSPATIALES
Call Details Starting Grant (StG), PE8, ERC-2014-STG
Summary Aeroelastic instabilities are at the origin of large deformations of structures and are limiting the capacities of products in various industrial branches such as aeronautics, marine industry, or wind electricity production. If suppressing aeroelastic instabilities is an ultimate goal, a paradigm shift in the technological development is to take advantage of these instabilities to achieve others objectives, as reducing the drag of these flexible structures. The ground-breaking challenges addressed in this project are to design fundamentally new theoretical methodologies for (i) describing mathematically aeroelastic instabilities, (ii) suppressing them and (iii) using them to reduce mean drag of structures at a low energetic cost. To that aim, two types of aeroelastic phenomena will be specifically studied: the flutter, which arises as a result of an unstable coupling instability between two stable dynamics, that of the structures and that the flow, and vortex-induced vibrations which appear when the fluid dynamics is unstable. An aeroelastic global stability analysis will be first developed and applied to problems of increasing complexity, starting from two-dimensional free-vibrating rigid structures and progressing towards three-dimensional free-deforming elastic structures. The control of these aeroelastic instabilities will be then addressed with two different objectives: their suppression or their use for flow control. A theoretical passive control methodology will be established for suppressing linear aeroelastic instabilities, and extended to high Reynolds number flows and experimental configurations. New perturbation methods for solving strongly nonlinear problems and adjoint-based control algorithm will allow to use these aeroelastic instabilities for drag reduction. This project will allow innovative control solutions to emerge, not only in flutter or vortex-induced vibrations problems, but also in a much broader class of fluid-structure problems.
Summary
Aeroelastic instabilities are at the origin of large deformations of structures and are limiting the capacities of products in various industrial branches such as aeronautics, marine industry, or wind electricity production. If suppressing aeroelastic instabilities is an ultimate goal, a paradigm shift in the technological development is to take advantage of these instabilities to achieve others objectives, as reducing the drag of these flexible structures. The ground-breaking challenges addressed in this project are to design fundamentally new theoretical methodologies for (i) describing mathematically aeroelastic instabilities, (ii) suppressing them and (iii) using them to reduce mean drag of structures at a low energetic cost. To that aim, two types of aeroelastic phenomena will be specifically studied: the flutter, which arises as a result of an unstable coupling instability between two stable dynamics, that of the structures and that the flow, and vortex-induced vibrations which appear when the fluid dynamics is unstable. An aeroelastic global stability analysis will be first developed and applied to problems of increasing complexity, starting from two-dimensional free-vibrating rigid structures and progressing towards three-dimensional free-deforming elastic structures. The control of these aeroelastic instabilities will be then addressed with two different objectives: their suppression or their use for flow control. A theoretical passive control methodology will be established for suppressing linear aeroelastic instabilities, and extended to high Reynolds number flows and experimental configurations. New perturbation methods for solving strongly nonlinear problems and adjoint-based control algorithm will allow to use these aeroelastic instabilities for drag reduction. This project will allow innovative control solutions to emerge, not only in flutter or vortex-induced vibrations problems, but also in a much broader class of fluid-structure problems.
Max ERC Funding
1 377 290 €
Duration
Start date: 2015-07-01, End date: 2020-06-30
